The influence of Harmonia axyridis morbidity on 2-Isopropyl-3-methoxypyrazine in 'Cabernet Sauvignon' wine

Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae; the Multicolored Asian Lady Beetle; MALB) is a vineyard pest in many winemaking regions of the world due to its ability to taint juice and wine (‘ladybug taint’) through excretion or extraction of 2-isopropyl-3-methoxypyrazine (IPMP) when the beetles are incorporated with the grapes at harvest. A common vineyard intervention is the use of insecticidal sprays and the resulting dead beetles are often incorporated in with the harvested fruit. The main objective of this study was to quantify the impact of dead MALB on IPMP concentrations in red wine. Duplicate 'Cabernet Sauvignon' wines were produced with the addition of 10 beetles·l-1 juice, added either live or at 1, 3, 7, or 60-days postmortem. A control wine with no added beetles was included. IPMP concentration was substantially higher in live-beetle wines, and decreased to base-line levels at approximately 6.5 days post-mortem. These results should assist in decisions on viticultural interventions, such as timing of insecticidal sprays, as well as the establishment of grape quality parameters.

Dual-modality gene reporter for in vivo imaging

The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth penetration, spatial resolution, and sensitivity. We describe here a gene reporter, based on the organic anion transporting protein Oatp1a1, which mediates uptake of a clinically approved, Gd(3+)-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T1-weighted magnetic resonance images acquired in vivo. The maximum signal enhancement obtained so far is more than double that produced by MRI gene reporters described previously. Exchanging the Gd(3+) ion for the radionuclide, (111)In, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging

Protocol for the 'e-Nudge trial' : a randomised controlled trial of electronic feedback to reduce the cardiovascular risk of individuals in general practice [ISRCTN64828380]

Background: Cardiovascular disease (including coronary heart disease and stroke) is a major cause of death and disability in the United Kingdom, and is to a large extent preventable, by lifestyle modification and drug therapy. The recent standardisation of electronic codes for cardiovascular risk variables through the United Kingdom's new General Practice contract provides an opportunity for the application of risk algorithms to identify high risk individuals. This randomised controlled trial will test the benefits of an automated system of alert messages and practice searches to identify those at highest risk of cardiovascular disease in primary care databases. Design: Patients over 50 years old in practice databases will be randomised to the intervention group that will receive the alert messages and searches, and a control group who will continue to receive usual care. In addition to those at high estimated risk, potentially high risk patients will be identified who have insufficient data to allow a risk estimate to be made. Further groups identified will be those with possible undiagnosed diabetes, based either on elevated past recorded blood glucose measurements, or an absence of recent blood glucose measurement in those with established cardiovascular disease. Outcome measures: The intervention will be applied for two years, and outcome data will be collected for a further year. The primary outcome measure will be the annual rate of cardiovascular events in the intervention and control arms of the study. Secondary measures include the proportion of patients at high estimated cardiovascular risk, the proportion of patients with missing data for a risk estimate, and the proportion with undefined diabetes status at the end of the trial

Quantifying normal human brain metabolism using hyperpolarized [1– 13 C]pyruvate and magnetic resonance imaging

Hyperpolarized 13 C Magnetic Resonance Imaging ( 13 C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1– 13 C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13 C images demonstrated 13 C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k PL ) for exchange of the hyperpolarized 13 C label between [1– 13 C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s −1 and the apparent rate constant (k PB ) for the irreversible flux of [1– 13 C]pyruvate to [ 13 C]bicarbonate was 0.002 ± 0.002 s −1 . Imaging also revealed that [1– 13 C]pyruvate, [1– 13 C]lactate and [ 13 C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1– 13 C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies

Assessing Oxidative Stress in Tumors by Measuring the Rate of Hyperpolarized [1-13^{13}C] Dehydroascorbic Acid Reduction Using 13^{13}C Magnetic Resonance Spectroscopy

Rapid cancer cell proliferation promotes the production of reducing equivalents, which counteract the effects of relatively high levels of reactive oxygen species (ROS). ROS levels increase in response to chemotherapy and cell death while an increase in antioxidant capacity can confer resistance to chemotherapy and is associated with an aggressive tumor phenotype. The pentose phosphate pathway (PPP) is a major site of NADPH production in the cell, which is used to maintain the main intracellular antioxidant, glutathione, in its reduced state. Previous studies have shown that the rate of hyperpolarized [1-$^{13}$C]dehydroascorbic acid (DHA) reduction, which can be measured $\textit{in vivo}$ using non-invasive $^{13}$C magnetic resonance spectroscopic imaging, is increased in tumors and that this is correlated with the levels of reduced glutathione. We show here that the rate of hyperpolarized [1-$^{13}$C]DHA reduction is increased in tumors that have been oxidatively pre-stressed by depleting the glutathione pool by buthionine sulfoximine treatment. This increase was associated with a corresponding increase in PPP flux, assessed using $^{13}$C-labeled glucose, and an increase in glutaredoxin activity, which catalyzes the glutathione-dependent reduction of DHA. These results show that the rate of DHA reduction does not depend only on the level of reduced glutathione, but also on the rate of NADPH production, contradicting the conclusions of some previous studies. Hyperpolarized [1-$^{13}$C]DHA can be used therefore to assess the capacity of tumor cells to resist oxidative stress in vivo. However, DHA administration resulted in transient respiratory arrest and cardiac depression, which may prevent translation to the clinic.Work in K.M. Brindle’s laboratory is supported by a Cancer Research UK Programme grant (17242) and the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465). K.N. Timm was in receipt of MRC and Cancer Research UK studentships, B.W.C. Kennedy and P. Dzien Cancer Research UK studentships and F. Bulat a CRUK -EPSRC Imaging Centre imaging center studentship. I. Marco -Rius acknowledges the European Union Seventh Framework Programme (FP7/2007-2013) for support under the M arie Curie Initial Training Network METAFLUX (project number 264780)